Chronic blepharitis is one of the most common conditions seen in the ophthalmologists office but is difficult to treat effectively. The disease is an extremely complex condition that manifests several different and overlapping arrays of signs and symptoms. Symptoms can include crusting of the lid margin, itching and burning eyelids, or lid inflammation and swelling, but signs can also include conjunctival inflammation and localized corneal damage. There is substantial evidence involving meibomian glands in several forms of this disease, especially the glandular lipid secretions. Because the meibomian gland lipid secretions form the outer layer of the tear film, the applicant's research has focused on certain unique characteristics of these lipids.This research project focuses on human subjects rather than animal models. This laboratory is the only one in the world doing lipid biochemical analysis of these secretions in health and disease. Patients with all types of chronic blepharitis are being thoroughly evaluated from a clinical and laboratory standpoint. This has led to the development of a classification system that is based not only on signs and symptoms but also on biochemical and microbial parameters. Evidence to date indicates lipid-lipid, lipid- bacterial, and bacterial exoenzyme-lipid interactions. The basic premise underlying this research is that certain biochemical changes of meibomian gland lipids cause many signs directly, while lipid composition itself predisposes secretions to other changes resulting from microbial activity or other factors. Thus, meibomian secretions are being evaluated biochemically and biophysically to determine the composition and properties of these secretions in normal individuals and in patients with chronic blepharitis. Because samples are small and the lipids are complex, gas chromatography - mass spectrometry is now being employed for analytical purposes. High pressure liquid chromatography is also used in order to achieve effective initial characterizations. Biophysical evaluations will utilize a microscope hot stage as well as techniques to characterize lipid layer film properties. In addition, isolated bacteria have been tested for production of specific exoenzymes such as lipases and esterases which could produce secondary lipid changes. Finally, secondary effects related to drugs and drug therapy will be evaluated since lipid analyses and microbial assays suggest that these may be quite important. Clinical trials will eventually be performed, based on these evaluations, thus permitting the ophthalmologist to select specific therapeutic treatments based on clinical signs and simple biochemical or microbial assays.